Dovitinib lactate (CHIR-258 lactate)

Dovitinib is a multi-kinase inhibitor.¹ It inhibits the receptor tyrosine kinases FLT3, CSF1R, and c-Kit (IC₅₀s = 1, 36, and 2 nM, respectively), as well as FGFR1, FGFR3, VEGFR1-3, PDFGRα, and PDGFRβ (IC₅₀s = 8, 9, 10, 13, 8, 27, and 210 nM, respectively). Dovitinib inhibits proliferation of human multiple myeloma cell lines expressing mutant, but not wild-type, FGFR3 (IC₅₀s = 90-550 and >2,500 nM, respectively). It decreases FGF-induced ERK1/2 phosphorylation and induces apoptosis in patient-derived multiple myeloma cells when used at a concentration of 500 nM. Dovitinib (3-300 mg/kg for eight days) inhibits bFGF-induced angiogenesis in a Matrigel^? plug assay in mice.² It reduces tumor growth in KM12L4A colon, DU145 prostate, and MV4-11 acute myelogenous leukemia mouse xenograft models with ED₅₀ values of 17, 23, and 3 mg/kg per day, respectively.

1.Trudel, S., Li, Z.H., Wei, E., et al.CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myelomaBlood105(7)2941-2948(2005) 2.Renhowe, P.A., Pecchi, S., Shafer, C.M., et al.Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A novel class of receptor tyrosine kinase inhibitorsJ. Med. Chem.52(2)278-292(2009)